Clinics and Research in Hepatology and Gastroenterology (2015) 39, e23—e24
Available online at
ScienceDirect www.sciencedirect.com
LETTER TO THE EDITOR Successful Eltrombopag treatment of refractory idiopathic thrombocytopenic purpura associated with Crohn disease Dear Editor, The occurrence of immune thrombocytopenic purpura (ITP) with inflammatory bowel disease (IBD) is rare. Particularly, reports of the association of Crohn disease (CD) and ITP are few. Approximately 0.1—0.48% of ulcerative colitis patients may present with ITP whilst less than 10 patients
Table 1
have been described with CD [1]. We herein report the case of a 25-year-old female who presented for a refractory CD associated with ITP. The patient presented to our department with a past medical history of an ileocecal CD refractory to treatment with azathioprine, sulfasalazine, mesalmine and infliximab. The patient refused any surgical option and her CD inflammatory flairs were partially controlled with methotrexate. She presented to our emergency department for an incidental discovery of a low platelet count. Her physical exam was unremarkable. Laboratory evaluation was only relevant for a platelet count of 15,000/mm3 . An extensive work-up retained the diagnosis of ITP. She received
Case reports of Crohn disease and immune thrombocytopenic purpura.
Study
Patient
Onset of ITP after CD
Location of CD
Treatment of CD
Response to steroids
Platelets antibodies
Treatment of ITP
Kosmo et al., 1986 [2] Manzano et al., 1996 [5] Zlatanic et al., 1997 [6] Arruda et al., 1997 [7] Baudard et al., 1998 [10]
65 F
+28 years
Colon
ND
Transient
+
54 M
—7 months
ND
+
+
22 F
+6 weeks
Colon, distal ileum Colon
Splenectomy, colectomy Corticosteroids
ND
+
ND
Corticosteroids
43 M
—2 months
Colon
ND
+
ND
Corticosteroids
19 F
Concomitant
Colon, distal ileon
ND
Transient
—
Boyne et al., 2000 [1] Kuloglu et al., 2005 [9]
17 F
+9 years
Colon
—
—
6M
—2 years
Transient
ND
Splenectomy
Tsibouris et al., 2006 [3]
44 M
+1.5 months
Corticosteroids Azathioprine
+
+
Corticosteroids, IVIG
Shaaban et al., 2013 [8]
57 M
+4 years
Oesophagus, distal ileon, colon, rectum Cecum, ascending colon, distal sigmoide Gastric
Left hemicolectomy Corticosteroids Mesalamin
Splenectomy, lost of follow-up IVIG
Mesalamine
+
+
Corticosteroids
CD: Crohn’s disease; F: female; ITP: idiopathic thrombocytopenic purpura; M: male; ND: not determined. http://dx.doi.org/10.1016/j.clinre.2014.10.011 2210-7401/© 2014 Elsevier Masson SAS. All rights reserved.
e24 rituximab, immunoglobulin and corticosteroids for a month and they were found ineffective; her platelet count fluctuated between 20,000—65,000/mm3 . The patient was splenectomised but the platelets remained in the low range 9000—35,000/mm3 . Eltrombopag 50 mg once daily was then introduced. After one week, the platelets increased to 65,000/mm3 and the count normalized in one month. The association of ITP and IBD was first described by Kosmo et al. in 1986, it is rare and only few cases are reported [2]. Multiple theories describe this association. Hypothetically, active IBD increases the exposure of the humoral immune system to colonic antigens. Thus, it increases anti-platelets antibodies formation and induces an ITP [3]. Another theory explains the absence of autoimmune antibodies and resistance to steroids by the destruction of sequestrated platelets sequestrated in colonic vasculature [1]. Both of these theories require a severe, uncontrollable or refractory CD with continuous inflammatory flairs. Based on the recognized consensus guidelines of the management of ITP, the first line treatment consists of steroids and intravenous immune globulin (IVIG). This initial treatment has an initial response rate of up to 80%. In case of failure, splenectomy or rituximab are indicated. Eltrombopag, thrombopoietin receptor agonist, is indicated in third line [4]. It acts by stimulating the production of megakaryocytes and eventually platelets. This treatment does not cause remission of the disease and maintenance therapy is required [4]. Literature reports 9 cases that associate ITP to CD. ITP control was achieved with corticosteroids in four patients [5—8], IVIG in two cases [1,3], splenectomy in one patient [9], colectomy in another [2] and one patient was lost of view [10] (Table 1). Our particular patient had both ITP and CD refractory to medical treatment. The introduction of eltrombopag allowed normalization of the platelet count albeit an incomplete control of CD, rendering this drug a first line option in cases of refractory CD associated to ITP.
Disclosure of interest
Letter to the editor
References [1] Boyne MS, Dye KR. Crohn’s colitis and idiopathic thrombocytopenic purpura. Postgrad Med J 2000;76(895):299—300. [2] Kosmo MA, Bordin G, Tani P, McMillan R. Immune thrombocytopenia and Crohn’s disease. Ann Intern Med 1986;104(1):136. [3] Tsibouris P, Kapsoritakis AN, Bouronikou E, Boulbou M, Kyriakou D, Potamianos SP. Crohn’s disease associated with severe autoimmune thrombocytopenic purpura. Inflamm Bowel Dis 2006;12(12):1188—9. [4] Zeng Y, Duan X, Xu J, Ni X. TPO receptor agonist for chronic idiopathic thrombocytopenic purpura. Cochrane Database Syst Rev 2011;(7):CD008235. [5] Manzano ML, Yela C, Castellano G, Rodriguez S, Solis JA. Idiopathic thrombocytopenic purpura and pancytopenia in a patient with Crohn’s disease: a new association. Am J Gastroenterol 1996;91(8):1678—9. [6] Zlatanic J, Korelitz BI, Wisch N, Kim P, Ammirati M, Schwarz S, et al. Inflammatory bowel disease and immune thrombocytopenic purpura: is there a correlation? Am J Gastroenterol 1997;92(12):2285—8. [7] Arruda VR, Montes CG, Sevá-Pereira A, Annicchino-Bizzacchi JM. Association of severe autoimmune thrombocytopenic purpura and Crohn’s disease. Am J Gastroenterol 1997;92(10):1948—9. [8] Shaaban H, Maroules M. A rare case of gastric Crohn’s disease associated with immune thrombocytopenic purpura. J Crohns Colitis 2013;7(9):e401—2. [9] Kulo˘ glu Z, Kansu A, Demirc ¸eken F, Ileri T, Ertem M, Girgin N. The association of chronic recurrent immune thrombocytopenic purpura and Crohn’s disease. Inflamm Bowel Dis 2005;11(10):950—1. [10] Baudard M, Molina T, Benfiguig K, Bethoux JP, Zittoun R. Idiopathic thrombocytopenic purpura associated with Crohn’s disease. Haematologica 1998;83(1):92—3.
Elie El Rassy ∗ Hampig Raphael Kourie William Nehme Samuel Georges Elie Haddad Roy Nasnas Fadi Nasr Faculty of Medicine, Saint Joseph University, Beirut, Lebanon ∗
The authors declare that they have no conflicts of interest concerning this article.
Corresponding author. Tel.: +9613690432. E-mail address: [email protected] (E. El Rassy) Available online 13 November 2014
Available online at
ScienceDirect www.sciencedirect.com
LETTER TO THE EDITOR Successful Eltrombopag treatment of refractory idiopathic thrombocytopenic purpura associated with Crohn disease Dear Editor, The occurrence of immune thrombocytopenic purpura (ITP) with inflammatory bowel disease (IBD) is rare. Particularly, reports of the association of Crohn disease (CD) and ITP are few. Approximately 0.1—0.48% of ulcerative colitis patients may present with ITP whilst less than 10 patients
Table 1
have been described with CD [1]. We herein report the case of a 25-year-old female who presented for a refractory CD associated with ITP. The patient presented to our department with a past medical history of an ileocecal CD refractory to treatment with azathioprine, sulfasalazine, mesalmine and infliximab. The patient refused any surgical option and her CD inflammatory flairs were partially controlled with methotrexate. She presented to our emergency department for an incidental discovery of a low platelet count. Her physical exam was unremarkable. Laboratory evaluation was only relevant for a platelet count of 15,000/mm3 . An extensive work-up retained the diagnosis of ITP. She received
Case reports of Crohn disease and immune thrombocytopenic purpura.
Study
Patient
Onset of ITP after CD
Location of CD
Treatment of CD
Response to steroids
Platelets antibodies
Treatment of ITP
Kosmo et al., 1986 [2] Manzano et al., 1996 [5] Zlatanic et al., 1997 [6] Arruda et al., 1997 [7] Baudard et al., 1998 [10]
65 F
+28 years
Colon
ND
Transient
+
54 M
—7 months
ND
+
+
22 F
+6 weeks
Colon, distal ileum Colon
Splenectomy, colectomy Corticosteroids
ND
+
ND
Corticosteroids
43 M
—2 months
Colon
ND
+
ND
Corticosteroids
19 F
Concomitant
Colon, distal ileon
ND
Transient
—
Boyne et al., 2000 [1] Kuloglu et al., 2005 [9]
17 F
+9 years
Colon
—
—
6M
—2 years
Transient
ND
Splenectomy
Tsibouris et al., 2006 [3]
44 M
+1.5 months
Corticosteroids Azathioprine
+
+
Corticosteroids, IVIG
Shaaban et al., 2013 [8]
57 M
+4 years
Oesophagus, distal ileon, colon, rectum Cecum, ascending colon, distal sigmoide Gastric
Left hemicolectomy Corticosteroids Mesalamin
Splenectomy, lost of follow-up IVIG
Mesalamine
+
+
Corticosteroids
CD: Crohn’s disease; F: female; ITP: idiopathic thrombocytopenic purpura; M: male; ND: not determined. http://dx.doi.org/10.1016/j.clinre.2014.10.011 2210-7401/© 2014 Elsevier Masson SAS. All rights reserved.
e24 rituximab, immunoglobulin and corticosteroids for a month and they were found ineffective; her platelet count fluctuated between 20,000—65,000/mm3 . The patient was splenectomised but the platelets remained in the low range 9000—35,000/mm3 . Eltrombopag 50 mg once daily was then introduced. After one week, the platelets increased to 65,000/mm3 and the count normalized in one month. The association of ITP and IBD was first described by Kosmo et al. in 1986, it is rare and only few cases are reported [2]. Multiple theories describe this association. Hypothetically, active IBD increases the exposure of the humoral immune system to colonic antigens. Thus, it increases anti-platelets antibodies formation and induces an ITP [3]. Another theory explains the absence of autoimmune antibodies and resistance to steroids by the destruction of sequestrated platelets sequestrated in colonic vasculature [1]. Both of these theories require a severe, uncontrollable or refractory CD with continuous inflammatory flairs. Based on the recognized consensus guidelines of the management of ITP, the first line treatment consists of steroids and intravenous immune globulin (IVIG). This initial treatment has an initial response rate of up to 80%. In case of failure, splenectomy or rituximab are indicated. Eltrombopag, thrombopoietin receptor agonist, is indicated in third line [4]. It acts by stimulating the production of megakaryocytes and eventually platelets. This treatment does not cause remission of the disease and maintenance therapy is required [4]. Literature reports 9 cases that associate ITP to CD. ITP control was achieved with corticosteroids in four patients [5—8], IVIG in two cases [1,3], splenectomy in one patient [9], colectomy in another [2] and one patient was lost of view [10] (Table 1). Our particular patient had both ITP and CD refractory to medical treatment. The introduction of eltrombopag allowed normalization of the platelet count albeit an incomplete control of CD, rendering this drug a first line option in cases of refractory CD associated to ITP.
Disclosure of interest
Letter to the editor
References [1] Boyne MS, Dye KR. Crohn’s colitis and idiopathic thrombocytopenic purpura. Postgrad Med J 2000;76(895):299—300. [2] Kosmo MA, Bordin G, Tani P, McMillan R. Immune thrombocytopenia and Crohn’s disease. Ann Intern Med 1986;104(1):136. [3] Tsibouris P, Kapsoritakis AN, Bouronikou E, Boulbou M, Kyriakou D, Potamianos SP. Crohn’s disease associated with severe autoimmune thrombocytopenic purpura. Inflamm Bowel Dis 2006;12(12):1188—9. [4] Zeng Y, Duan X, Xu J, Ni X. TPO receptor agonist for chronic idiopathic thrombocytopenic purpura. Cochrane Database Syst Rev 2011;(7):CD008235. [5] Manzano ML, Yela C, Castellano G, Rodriguez S, Solis JA. Idiopathic thrombocytopenic purpura and pancytopenia in a patient with Crohn’s disease: a new association. Am J Gastroenterol 1996;91(8):1678—9. [6] Zlatanic J, Korelitz BI, Wisch N, Kim P, Ammirati M, Schwarz S, et al. Inflammatory bowel disease and immune thrombocytopenic purpura: is there a correlation? Am J Gastroenterol 1997;92(12):2285—8. [7] Arruda VR, Montes CG, Sevá-Pereira A, Annicchino-Bizzacchi JM. Association of severe autoimmune thrombocytopenic purpura and Crohn’s disease. Am J Gastroenterol 1997;92(10):1948—9. [8] Shaaban H, Maroules M. A rare case of gastric Crohn’s disease associated with immune thrombocytopenic purpura. J Crohns Colitis 2013;7(9):e401—2. [9] Kulo˘ glu Z, Kansu A, Demirc ¸eken F, Ileri T, Ertem M, Girgin N. The association of chronic recurrent immune thrombocytopenic purpura and Crohn’s disease. Inflamm Bowel Dis 2005;11(10):950—1. [10] Baudard M, Molina T, Benfiguig K, Bethoux JP, Zittoun R. Idiopathic thrombocytopenic purpura associated with Crohn’s disease. Haematologica 1998;83(1):92—3.
Elie El Rassy ∗ Hampig Raphael Kourie William Nehme Samuel Georges Elie Haddad Roy Nasnas Fadi Nasr Faculty of Medicine, Saint Joseph University, Beirut, Lebanon ∗
The authors declare that they have no conflicts of interest concerning this article.
Corresponding author. Tel.: +9613690432. E-mail address: [email protected] (E. El Rassy) Available online 13 November 2014
